TIGIT drug from iTeos shrinks lung tumors in trial

Small biotechnology company iTeos Therapeutics could succeed where larger drugmakers have fallen short, should study results it presented Saturday at a cancer research conference hold up in further testing.

The results, from a mid-stage clinical trial, show that adding iTeos’ drug to an approved GSK immunotherapy shrank lung tumors in roughly twice as many people as GSK’s therapy alone. They have been anticipated since May, when iTeos said the two-drug regimen surpassed its expectations treating a common form of lung cancer.

ITeos may face some questions on the safety of combining the two medicines, which both ramp up the body’s immune attack on tumors. Three patients in the trial died from immune-related inflammation that study investigators judged as related to treatment. All three were in study arms involving ITeos’ drug; none of the 32 trial participants given only GSK’s therapy, Jemperli, died from treatment-related side effects.

This kind of inflammatory reaction is a known risk of medicines like Jemperli and has resulted in deaths in other immunotherapy studies. ITeos, in an email to BioPharma Dive, said that it expects the safety profile of its regimen to be in line with existing immunotherapy combinations.

ITeos’ drug has drawn attention in large part due to the protein that it targets. Called TIGIT, the protein is thought to stifle the immune response to cancer, suggesting that blocking it could supercharge the anti-tumor effects of Jemperli and other similar immunotherapies.

Pharmaceutical companies, among them Roche, Merck & Co., Gilead Sciences and Bristol Myers Squibb, have spent years chasing that hypothesis, with little to show for their efforts. Several important studies failed to show blocking TIGIT helps, sparking doubts about the target that led some companies to pull back on further research.

While early, iTeos’ data could rekindle some of that interest. The tumor responses it presented Saturday at the European Society for Medical Oncology’s annual meeting in Barcelona generally meet the bar Wall Street analysts had set for success.

In the trial, which enrolled 124 people with untreated advanced or metastatic non-small cell lung cancer, iTeos tested three doses of its drug, belrestotug, alongside Jemperli. Another group received Jemperli monotherapy. Initial overall response rates, which assess how much tumors shrink, ranged between 63% and 77% across the three combination arms, compared to 38% for Jemperli alone.

ITeos repeated tumor imaging scans four weeks or later following those initial responses. On this “confirmed” basis, overall response rates were roughly 60% in each of the combination groups, versus 28% for Jemperli.

“This is why we’re so excited to come to Barcelona,” said Michel Detheux, iTeos’ president and CEO. “We are really reaching a stage where we can confirm our best-in-class strategy.”

In notes to clients ahead of ESMO, analysts at Piper Sandler and Leerink Partners sketched out slightly different scenarios by which iTeos could claim a positive outcome. Christopher Raymond, at Piper Sandler, described the data “bogey” as response rates in the range of 55% to 60%. Leerink Partners’ Daina Graybosch set a somewhat higher range, of 60% to 70%.

Merck’s immunotherapy Keytruda, which is standard treatment for the group of lung cancer patients iTeos enrolled in its trial, is associated with overall response rates of around 40%. Both analysts thought iTeos would need to show response rates between 20 to 30 percentage points higher than that.

All of the responses recorded by iTeos were considered “partial,” meaning treatment did not completely eradicate tumors. ITeos also analyzed the amount of DNA shed by tumors and circulating in the blood, and found greater reductions at higher combination doses.